To evaluate TG gene variants and their effects on the clinical course of the disease in children with congenital hypothyroidism (CH) who are suspected to have thyroglobulin synthesis defect. The study was carried out in patients who were suspected to have thyroglobulin synthesis defect due to low serum thyroglobulin level and goiter at the time of diagnosis of CH. Peripheral blood samples were taken and hypothyroidism gene panel including 344 genes was amplified by PCR and sequenced using next-generation DNA sequencing (NGS) method. A total of four eligible cases were identified for genetic analysis, and variants were detected in all of them. In case 1, a previously reported homozygous c.638 + 5 G>A splice site variant was detected. In case 2, compound heterozygous variants including a previously reported nonsense variant c.7111 C>T, (p.Arg2371Ter) on the first allele and a novel nonsense variant c.5748 C>A, (p.Tyr1916Ter) on the second allele were detected. In case 3, a previously reported homozygous nonsense variant c.1888 C>T, (p.Gln630Ter) was detected. In case 4, a novel homozygous intronic variant c.6200-25T>G was detected. The distinctive phenotypic features of TG gene variants, which are one of the rare causes of dyshormonogenesis, provide an advantage in diagnosis. Therefore, we recommend genetic analysis in cases with low thyroglobulin levels and goiter. Our findings support that TG variants show a heterogeneous distribution over the whole gene. Since the relationship between TG gene variants and thyroid cancer, we suggest that clarification of TG gene variants is important in terms of early diagnosis of thyroid nodule and malignancy.

Background: Alpha-thalassemia is one of the most common hereditary hemoglobin disorders worldwide and is caused mainly by deletions in the α-globin gene cluster. Understanding the regional mutation spectrum is important for screening programs and genetic counseling. Methods: This retrospective study included 115 patients evaluated for suspected alpha-thalassemia in Antalya, Türkiye. Molecular analysis was performed using multiplex ligation-dependent probe amplification (MLPA) to detect deletions and duplications in the α-globin gene cluster. Hematological parameters and hemoglobin (Hb) fractions were analyzed and compared among mutation groups. Results: The most frequent mutation detected was the −α^3.7 deletion followed by the (−α)^20.5 deletion. Patients with compound heterozygous deletions demonstrated lower Hb, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) values compared with other groups. Significant correlations were observed between Hb levels and red blood cell (RBC), MCV, and MCH, while red cell distribution width (RDW) showed an inverse relationship. Conclusions: The results demonstrate that −α^3.7 and (−α)^20.5 are the predominant α-globin gene variants in the Antalya region. These findings contribute to the characterization of the α-thalassemia mutation spectrum in a clinical cohort and may help improve carrier screening strategies, prenatal diagnosis programs, and genetic counseling services.

Background and Objectives: Variation in RANK/RANKL/OPG signaling may contribute to rheumatoid arthritis (RA) heterogeneity. We examined whether recorded TNFRSF11A exon 5–flanking variant carrier status was associated with six-month clinical outcomes in treatment-naïve RA. Materials and Methods: This prospective cohort included 57 patients: 10 carriers and 47 non-carriers. The primary outcome was six-month DAS28-CRP. Welch tests, Fisher’s exact tests, effect sizes, 95% confidence intervals, and exploratory baseline-adjusted models were used; missing outcomes were not imputed. Results: Carriers had lower six-month DAS28-CRP than non-carriers (2.53 ± 0.98 [n=10] vs 2.85 ± 0.99 [n=37]) and lower CRP (6.58 ± 6.96 vs 7.59 ± 9.29 mg/L). DAS28-CRP < 2.6 occurred in 60.0% of carriers and 35.1% of non-carriers (OR, 2.769; 95% CI, 0.660–11.618). High activity, recorded deformity, and biologic initiation were 10.0% vs 35.1%, 10.0% vs 29.8%, and 20.0% vs 36.1%, respectively. The composite score was 3.60 ± 1.08 vs 2.83 ± 1.07 (d=0.720; p=0.064). The adjusted DAS28-CRP coefficient was −0.165 (95% CI, −0.850 to 0.520; p=0.629). Conclusions: The carrier pattern suggests a more favorable short-term RA profile, but remains hypothesis-generating and requires prospective validation.

AMAÇ: JAK2V617F mutasyonu pozitifliği kronik miyeloproliferatif neoplazilerin (KMPN) tanısı için ana kriterdir. Mutasyon yükünün belirlenmesi çoğu moleküler laboratuvarda standart bir tanı prosedürü haline gelmiştir, ancak KMPN tanısı için bir sınır değer belirtilmemektedir. Burada, JAK2V617F mutasyon yükü düşük ve yüksek olan miyeloproliferatif neoplazi ön tanılı hastaların klinik ve hematolojik parametreler açısından karşılaştırılması amaçlandı. GEREÇ VE YÖNTEM: Sağlık Bilimleri Üniversitesi Antalya Eğitim ve Araştırma Hastanesi tıbbi genetik kliniğinde 2019 - 2021 yılları arasında JAK2V617F mutasyonu pozitif olan 95 hasta retrospektif olarak analiz edildi. BULGULAR: Allel yükü düşük (≤%3) olan 46 hastanın %64'ü KMPN fenotipine sahipken, yüksek allel yükü (>%3) olan 49 hastanın %100'ü KMPN fenotipine sahipti. Her iki grup arasında eritrosit sayısı, hemoglobin düzeyi, ortalama eritrosit hacimleri arasında istatistiksel bir fark bulunmazken; lökosit, nötrofil ve trombosit yüksekliği JAK2V617F allel yükü >%3 olan grup lehine istatistiksel olarak anlamlı bulundu (p=0.007; p<0.001; p%3 olan tüm hastalara KMPN tanısı konulmuştur; bu nedenle, bu sınırın üzerindeki bir mutasyon yükü, miyeloproliferatif bir hastalığın varlığın göstergesi olarak kabul edilebilir. Düşük allel yüklü JAK2V617F mutasyonuna yaklaşımı tanımlamak için standardize edilmiş moleküler yöntemlerle prospektif olarak incelenen daha büyük hasta gruplarına sahip çalışmalara ihtiyaç vardır.